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MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis

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Abstract

Apomucins play important biological roles in cell–cell and cell–extracellular matrix interactions, in cell signaling, and in biological properties of cancer cells. Their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins, gel-forming components of viscoelastic mucus gels protecting the epithelia, includes mucins MUC2 and MUC6. Their principle function is to contribute in mucus formation by forming a tridimensional network via oligomerization domains to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and MUC6 in patients with gastric carcinoma. MUC2 and MUC6 expressions were detected immunohistochemically in gastric cancer biopsies using specific monoclonal antibodies. The results showed that in our gastric carcinoma cases, MUC2 expression was detected in 78.6% of cases. MUC2 expression is increased from well differentiated to moderately differentiated to poorly differentiated gastric adenocarcinoma. On the other hand, MUC6 was detected in 32% of cases. The expression of MUC2 is increasing, which is accompanied by an altered expression of MUC6 in gastric cancer. Therefore, it is concluded that the expression pattern of secreted mucins including MUC2 and MUC6 is altered apparently in gastric carcinoma.

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References

  1. Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol. 1995;57:607–34.

    Article  PubMed  CAS  Google Scholar 

  2. Wang R-Q, Fang D-C. Alterations of MUC1 and MUC3 expression in gastric carcinoma: relevance to patient clinicopathological features. J Clin Pathol. 2003;56:378–84.

    Article  PubMed  Google Scholar 

  3. Lau SK, Weiss LM, Chu PG. Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004;122:61–9.

    Article  PubMed  Google Scholar 

  4. Roessler K, Monig SP, Schneider PM, Hanisch FG, Landsberg S, Thiele J, Holscher AH, Dienes HP, Baldus SE. Co-expression of CDX2 and MUC2 in gastric carcinomas: correlations with clinico-pathological parameters and prognosis. World J Gastroenterol. 2005;11:3182–8.

    PubMed  CAS  Google Scholar 

  5. Kim HJ, Kim SH, Chae GB, Lee SJ, Kang CD. Increased expression of Mucin 5AC mRNA and decreased expression of epidermal growth factor receptor mRNA in gallstone patients. Tohoku J Exp Med. 2008;214:139–44.

    Article  PubMed  CAS  Google Scholar 

  6. Babu DS, Jayanthi V, Devaraj N, Reis CA, Devaraj H. Expression profile of mucins (Muc2, Muc5AC and Muc6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium. Mol Cancer. 2006;5:1476–4598.

    Article  Google Scholar 

  7. Wada R, Yamaguchi T, Tanizaki T. Mucin phenotypic expression and p53 gene abnormality of gastric superminute well differentiated adenocarcinoma. Reevaluation with relationship between histogeneis of well differentiated adenocarcinoma and intestinal metaplasia in distal stomach. J Carcinog. 2005;1:4–14.

    Google Scholar 

  8. Reis CA, David L, Carvalho F, Mandel U, de Bolos C, Mirgorodskaya E, Clausen H, Sobrinho-Simoes M. Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas. J Histochem Cytochem. 2000;48:377–88.

    Article  PubMed  CAS  Google Scholar 

  9. Lee HS, Lee HK, Kim HS, Yang HK, Kim YI, Kim WH. MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. Cancer. 2001;92:1427–34.

    Article  PubMed  CAS  Google Scholar 

  10. Cornfield AP, Carroll D, Myerscough N, Probert CS. Mucins in the gastrointestinal tract in health and disease. Front Biosci. 2001;6:1321–57.

    Article  Google Scholar 

  11. Pinto-de-Sousa J, David L, Reis CA, Gomes R, Silva L, Pimenta A. Mucins MUC1, MUC2, MUC5AC and MUC6 expression in the evaluation of differentiation and clinico-biological behavior of gastric carcinoma. Virchows Arch. 2002;440:304–10.

    Article  PubMed  CAS  Google Scholar 

  12. Shiroshita H, Watanabe H, Ajioka Y. Re-evaluation of mucin phenotypes of gastric minute well differentiated type adenocarcinoma using a series of HGM, Muc5AC, Muc6, M-GGMC, Muc2 and CD10 stains. Pathol Intern. 2004;54:311–21.

    Article  CAS  Google Scholar 

  13. Songun I, van de Velde CJ, Arends JW, Blok P, Grond AJ, Offerhaus GJ, Hermans J, van Krieken JH. Classification of gastric carcinoma using the Goseki system provides prognostic information additional to TNM staging. Cancer. 1999;85:2114–8.

    Article  PubMed  CAS  Google Scholar 

  14. Gurbuz Y, Kahlke V, Kloppel G. How do gastric carcinoma classification systems relate to mucin expression patterns? An immunohistochemical analysis in a series of advanced gastric carcinomas. Virchows Arch. 2002;440:505–11.

    Article  PubMed  Google Scholar 

  15. Reis CA, David L, Nielsen PA, et al. Immunohistochemical study of MUC5AC expression in human gastric carcinomas using a novel monoclonal antibody. Int J Cancer. 1997;74:112–21.

    Article  PubMed  CAS  Google Scholar 

  16. Reis CA, David L, Correa P, Carneiro F, de Bolos C, Garcia E, Mandel U, Clausen H, Sobrinho-Simoes M. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res. 1999;59:1003–7.

    PubMed  CAS  Google Scholar 

  17. Nogueira AM, Machado JC, Carneiro F, Reis CA, Gott P, Sobrinho–Simoes M. Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation. J Pathol. 1999;187:541–8.

    Article  PubMed  CAS  Google Scholar 

  18. Craanen ME, Blok P, Dekker W, Ferwerda J, Tytagt GN. Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa. Dig Dis Sci. 1991;36:1529–36.

    Article  PubMed  CAS  Google Scholar 

  19. Rokkas T, Filipe MI, Sladen GE. Detection of an increased of early gastric cancer in patients with intestinal metaplasia type III who are closely followed up. Gut. 1991;32:1110–3.

    Article  PubMed  CAS  Google Scholar 

  20. Sakamoto H, Yonezawa S, Utsunomiya T, et al. Mucin antigen expression in gastric carcinoma of young and old adults. Hum Pathol. 1997;28:1056–65.

    Article  PubMed  CAS  Google Scholar 

  21. Baldus SE, Zirbes TK, Engel S, Hanisch FG, Mönig SP, Lorenzen J, Glossmann J, Fromm S, Thiele J, Pichlmaier H, Dienes HP. Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer. 1998;79:133–8.

    Article  PubMed  CAS  Google Scholar 

  22. Hamilton SR, Aaltonen LA. World Health Organization classification of tumors. Pathology and genetics of tumors of the digestive system. Lyon: IARC Press; 2000. p. 37–67.

  23. Dixon MF, Genta RM, Yardley H, Lorea P. Classification and grading of gastritis: the Updated Sydney System. International workshop on the histopathology of gastritis, Houton 1994. Am J Surg Pathol. 1996;20:1161–81.

    Article  PubMed  CAS  Google Scholar 

  24. Senapati S, Das S, Batra SK. Mucin-interacting proteins: from function to therapeutics. Trends Biochem Sci. 2010;35:236–45.

    Article  PubMed  CAS  Google Scholar 

  25. Yonezawa S, Sato E. Expression of mucin antigens in human cancers and its relationship with malignancy potential. Pathol Int. 1997;47:813–30.

    Article  PubMed  CAS  Google Scholar 

  26. Corra PA. A human model of gastric carcinogenesis. Cancer Res. 1988;48:3554–60.

    Google Scholar 

  27. Reis CA, David L, Correa P, Carneiro F, de Bolos C, Garcia E, Mandel U, Clausen H, Sobrinho-Simoes M. Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression. Cancer Res. 1999;59:1003–7.

    PubMed  CAS  Google Scholar 

  28. Lesuffleur T, Zweibaum A, Real FX. Mucins in normal and neoplastic human gastrointestinal tissues. Crit Rev Oncol Hematol. 1994;17:153–80.

    Article  PubMed  CAS  Google Scholar 

  29. Kobayashi K, Okamoto T, Takayama S. Genetic instability in intestinal metaplasia is a frequent event leading to well differentiated early adenocarcinoma of the stomach. Eur J Cancer. 2000;36:113–9.

    Article  Google Scholar 

  30. Filipe MI, Linehan JM, Durrant LG, Price MR, Smeeton NC, Pathak S, Swallow DM. Expression of a peptide epitope of the colonic mucin MUC2 in precursor lesion to gastric carcinoma. Eur J Cancer Prev. 1996;5:287–95.

    Article  PubMed  CAS  Google Scholar 

  31. Reis CA, Sorensen T, Mandel U, David L, Mirgorodskaya E, Roepstorff P, Kihlberg J, Stig-Hansen J-E, Clausen H. Development and characterization of an antibody directed to an α-N-acetyl-D-galactosamine glycosylated MUC2 peptide. Glycoconj J. 1998;15:51–62.

    Article  PubMed  CAS  Google Scholar 

  32. De Bolos C, Garrido M, Real FX. MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach. Gastroenterology. 1995;109:723–34.

    Article  PubMed  Google Scholar 

  33. Ho SB, Shekels LL, Toribara NW, Kim YS, Lyftogt C, Cherwitz DL, Niehans GA. Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. Cancer Res. 1995;55:2681–90.

    PubMed  CAS  Google Scholar 

  34. Carrato C, Balague C, De Bolos C, Gonzalez E, Gambus G, Planas J, Perini JM, Andreu D, Real FX. Differential apomucin expression in normal and neoplastic human gastrointestinal tissues. Gastroenterology. 1994;107:160–72.

    PubMed  CAS  Google Scholar 

  35. Leteurtre E, Zerimech F, Piessen G, Wacrenier A, Leroy X, Copin MC, Mariette C, Aubert JP, Porchet N, Buisine MP. Relationships between mucinous gastric carcinoma, MUC2 expression and survival. World J Gastroenterol. 2006;21:3324–31.

    Google Scholar 

  36. Tajima Y, Shimoda T, Nakanishi Y, Yokoyama N, Tanaka T, Shimizu K, Saito T, Kawamura M, Kusano M, Kumagai K. Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions. Oncology. 2001;61:212–20.

    Article  PubMed  CAS  Google Scholar 

  37. Machado JC, Nogueira AM, Carneiro F, Reis CA, Sobrinho-Simões M. Gastric carcinoma exhibits distinct types of cell differentiation: an immunohistochemical study of trefoil peptides (TFF1 and TFF2) and mucins (MUC1, MUC2, MUC5AC, and MUC6). J Pathol. 2000;190:437–43.

    Article  PubMed  CAS  Google Scholar 

  38. Akyürek N, Akyol G, Dursun A, Yamac D, Gunel N. Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis. Pathol Res Pract. 2002;198:665–74.

    Article  PubMed  Google Scholar 

  39. Wakatsuki K, Yamada Y, Narikiyo M, Ueno M, Takayama T, Tamaki H, Miki K, Matsumoto S, Enomoto K, Yokotani T, Nakajima Y. Clinicopathological and prognostic significance of mucin phenotype in gastric cancer. J Surg Oncol. 2008;2:124–9.

    Article  Google Scholar 

  40. Zheng HC, Li XH, Hara T, Masuda S, Yang XH, Guan YF, Takano Y. Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch. 2008;5:525–34.

    Article  Google Scholar 

  41. Kocer B, Soran A, Kiyak G, Erdogan S, Eroglu A, Bozkurt B, Solak C, Cengiz O. Prognostic significance of mucin expression in gastric carcinoma. Dig Dis Sci. 2004;49:954–64.

    Article  PubMed  CAS  Google Scholar 

  42. Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, Tanaka S, Irimura T, Kim YS, Sato E. Expression of MUC1 and MUC2 mucins in gastric carcinoma: its relationship with the prognosis of the patients. Clin Cancer Res. 1998;4:2605–14.

    PubMed  CAS  Google Scholar 

  43. Kusano M, Kumagai K. Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions. Oncology. 2001;61:212–20.

    Article  PubMed  Google Scholar 

  44. Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB, Büller HA, Dekker J, Van Seuningen I, Renes IB, Einerhand AW. MUC2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology. 2006;131:117–29.

    Article  PubMed  Google Scholar 

  45. Hasnain SZ, Wang H, Ghia J–E, Haq N, Deng Y, Velcich A, Grencis RK, Thornton DJ, Khan WI. Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection. Gastroentrology. 2010;138:1763–71.

    Article  CAS  Google Scholar 

  46. Boland CR, Montgomery CK, Kim YS. Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation. Proc Natl Acad Sci USA. 1982;79:2051–5.

    Article  PubMed  CAS  Google Scholar 

  47. Buisine MP, Desreumaux P, Debailleul V, et al. Abnormalities in mucin gene expression in Crohn’s disease. Inflamm Bowel Dis. 1999;5:24–32.

    Article  PubMed  CAS  Google Scholar 

  48. Crabtree JE, Heatley RV, Losowsky MS. Glycoprotein synthesis and secretion by cultured small intestinal mucosa in coeliac disease. Gut. 1989;30:1339–43.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Mahmoud Lotfy.

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Khattab, AZ.M., Nasif, W.A. & Lotfy, M. MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis. Med Oncol 28 (Suppl 1), 207–213 (2011). https://doi.org/10.1007/s12032-010-9699-5

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